Amino acid chelates are generally produced by the reaction between .alpha.-amino acids and metal ions having a valence of two or more to form a heterocyclic ring structure. In such a reaction, the positive electrical charge of the metal ion is neutralized by the electrons available through the carboxylate or free amino groups of the .alpha.-amino acid.
Traditionally, the term "chelate" has been loosely defined as a combination of a metallic ion bonded to one or more ligands forming heterocyclic ring structures. Under this definition, chelate formation through neutralization of the positive charges of the divalent metal ions may be through the formation of ionic, covalent or coordinate covalent bonding. An alternative and more contemporary definition of the term "chelate" requires that the metal ion be bonded to the ligand solely by coordinate covalent bonds forming the ring structure. In either case, both are definitions that describe a metal ion and a ligand forming a heterocyclic ring.
A chelate is a definite structure resulting from precise requirement of synthesis. Proper conditions must be present for chelation to take place, particularly under the more modern definition. These conditions include proper mole ratios of ligands to metal ions, pH and solubility of reactants. Generally, for chelation to occur, all components are dissolved in solution and are either ionized or of appropriate electronic configuration in order for coordinate covalent bonding and/or ionic bonding between the ligand and the metal ion to occur.
Chelation can be confirmed and differentiated from mixtures of components by infrared spectra through comparison of the stretching of bonds or shifting of absorption caused by bond formation. As applied in the field of mineral nutrition, there are two allegedly "chelated" products which are commercially utilized. The first is referred to as a "metal proteinate." The American Association of Feed Control officials (AAFCO) has defined a "metal proteinate" as the product resulting from the chelation of a soluble salt with amino acids and/or partially hydrolyzed protein. Such products are referred to as the specific metal proteinate, e.g., copper proteinate, zinc proteinate, etc.
The American Association of Feed Control Officials (AAFCO) has also issued a definition for an amino acid chelate. It is officially defined as the product resulting from the reaction of a metal ion from a soluble metal salt with amino acids with a mole ratio of one mole of metal to one to three (preferably two) moles of amino acids to form coordinate covalent bonds. The average weight of the hydrolyzed amino acids must be approximately 150 and the resulting molecular weight of the chelate must not exceed 800. The products are identified by the specific metal forming the chelate, e.g., iron amino acid chelate, copper amino acid chelate, zinc amino acid chelate, etc.
An "amino acid chelate," when properly formed, is a stable product having one or more five-membered rings formed by reaction between the carboxyl oxygen, and the .alpha.-amino group of an .alpha.-amino acid with the metal ion. Such a five-membered ring is defined by the metal atom, the carboxyl oxygen, the carbonyl carbon, the a-carbon and the .alpha.-amino nitrogen. The actual structure will depend upon the ligand to metal mole ratio and whether the carboxyl oxygen forms a coordinate covalent bond or an ionic bond with the metal ion. Generally, the ligand to metal mole ratio is at least 1:1 and is preferably 2:1 but, in certain instances, may be 3:1 or even 4:1. Most typically, an amino acid chelate may be represented at a ligand to metal ratio of 2:1 according to Formula 1 as follows: ##STR1##
In the above formula, the dashed lines represent coordinate covalent bonds, covalent bonds or ionic bonds and the solid lines represent covalent bonds or coordinate covalent bonds (i.e., bond between the metal and the .alpha.-amino groups). When R is H, the amino acid is glycine which is the simplest of the .alpha.-amino acids. However, R could be representative of any other of the other twenty or so naturally occurring amino acids derived from proteins. Regarding the sulfur-containing amino acids, when R is --CH.sub.2 --CH.sub.2 --S--CH.sub.3, the amino acid is methionine, and when R is CH.sub.2 --SH, the amino acid is cysteine. Further, two cysteine molecules bonded together by a disulfide bond form the amino acid cystine. Despite the different side chains, all of the amino acids have the same configuration for the positioning of the carboxyl oxygen and the .alpha.-amino nitrogen with respect to the metal ion. In other words, the chelate ring is defined by the same atoms in each instance.
The reason a metal atom can accept bonds over and above the oxidation state of the metal is due to the nature of chelation. For example, at the .alpha.-amino group of an amino acid, the nitrogen contributes to both of the electrons used in the bonding. These electrons fill available spaces in the d-orbitals forming a coordinate covalent bond. Thus, a metal ion with a normal valency of +2 can be bonded by four bonds when fully chelated. In this state, the chelate is completely satisfied by the bonding electrons and the charge on the metal atom (as well as on the overall molecule) is zero. As stated previously, it is possible that the metal ion be bonded to the carboxyl oxygen by either coordinate covalent bonds or ionic bonds. However, the metal ion is typically bonded to the .alpha.-amino group by coordinate covalent bonds only.
The structure, chemistry and bioavailability of amino acid chelates is well documented in the literature, e.g. Ashmead et al., Chelated Mineral Nutrition, (1982), Chas. C. Thomas Publishers, Springfield, Ill.; Ashmead et al., Intestinal Absorption of Metal Ions, (1985), Chas. C. Thomas Publishers, Springfield, Ill.; Ashmead et al., Foliar Feeding of Plants with Amino Acid Chelates, (1986), Noyes Publications, Park Ridge, N.J.; U.S. Pat. Nos. 4,020,158; 4,167,564; 4,216,143; 4,216,144; 4,599,152; 4,774,089; 4,830,716; 4,863,898 and others. Further, flavored effervescent mixtures of vitamins and amino acid chelates for administration to humans in the form of a beverage are disclosed in U.S. Pat. No. 4,725,427.
One advantage of amino acid chelates in the field of mineral nutrition is attributed to the fact that these chelates are readily absorbed in the mucosal cells by active transport or in plant cells as though they were solely amino acids. In other words, in the case of animal nutrition, the minerals are absorbed along with the amino acids as a single unit utilizing the amino acids as carrier molecules. Therefore, the problems associated with the competition of ions for active sites and the suppression of specific nutritive mineral elements by others are avoided.
Zinc (Zn) is an essential trace mineral that is present in nearly all animal cells, including humans. However, zinc is highly concentrated in specialized areas of the brain, pancreas and adrenal gland. Further, zinc has structural, enzymatic and regulatory roles in the body of animals. In fact, well over 70 enzymes require zinc for activity, including RNA polymerases. Further, zinc is essential for proper growth, tissue repair, sexual maturity (i.e., reproductive organs, prostate functions and male hormone activity), reproductive performance, blood stability, protein synthesis, digestion and metabolism of phosphorus, and immunity.
Deficiencies in zinc may result in delayed sexual maturity, prolonged healing of wounds, white spots on the finger nails, retarded growth, stretch marks, fatigue, decreased alertness, and susceptibility to infections. However, though deficiencies may take a part in causing the above heath-related issues, excessive zinc has been linked to impaired immune function, altered blood cholesterol levels, and a wide range of blood abnormalities. This being the case, it would be important for one to get his or her daily requirement of zinc by a source that is predictable regarding bioavailability and at a weight percentage that is advantageous.
The U.S. Recommended Daily Allowance (RDA) for zinc is as follows: for babies from birth to 1 year, 5 mg per day; for children 1 to 10 years, 10 mg per day; for men and boys 11 to 51 years, 15 mg per day; for women and girls 11 to 51 years, 12 mg per day; for pregnant women, 15 mg per day; for nursing mothers in the first 6 months, 19 mg per day; and for nursing mothers in the second 6 months, 16 mg per day.
Turning to the nourishment of non-human animals, the major sources of zinc approved by AAFCO for use in animal feed are zinc oxide and zinc sulfate. Zinc oxide is the most widely-used source of zinc in the animal feed industry because it has the highest zinc content and has been the most economical source of zinc on a per-unit basis. Zinc oxide suitable for animal use in feed is usually manufactured by the Waelz Kiln process. In the Waelz Kiln process, zinc-bearing ores are roasted, forming a zinc fume. The zinc fume is collected in a large collector and is densified. The very high temperatures used in this process drive off most of the residual heavy metals. Alternatively, zinc oxide for use in the feed industry may also be manufactured by the French process. The French process usually results in a higher zinc content (e.g. 78-80% zinc) than that produced by the Waelz Kiln process. However, the French process produces a powder that is more difficult to handle in animal feed mixes and is generally more expensive on a per-unit of zinc basis.
Zinc sulfate is also regularly used in animal feed products as an economic alternative to zinc oxide. Essentially, to make zinc sulfate, zinc is dissolved in sulfur-containing acid and spray dried. In either case, whether zinc oxide or zinc sulfate is used in an animal feed product, there are issues that work to prevent some of the zinc consumed by the animal from being bioavailable.
More recently, there has been a growing interest in compounds containing zinc and amino acids. For example, in U.S. Pat. No. 5,061,815, a zinc lysine complex is disclosed which also includes a halide, sulfate, phosphate, carbonate or acetate ion. This product is normally used in poultry and/or livestock rations. Particularly, the compound zinc lysine sulfate is commercially used and is alleged to provide rapid zinc absorption into the gastrointestinal tract of animals. The specific structure is comprised of one ion of zinc which is bound to one molecule of the amino acid lysine with an associated sulfate ion, i.e., 1:1 ligand to metal molar ratio.
Based upon what is known in the art presently, it would be useful to provide a zinc compound that is stable and is also more bioavailable than the inorganic zinc compounds previously known in the art. Further, it would be useful to provide a zinc compound that is formed by chelating zinc ions to a mixture glycine and a sulfur-containing amino acid, such that the weight percentage of zinc to the ligand may be more easily controlled and the zinc may be targeted to specific tissues or organs. These needs and others are fulfilled by the zinc amino acid chelate compositions of the present invention.